SYNTHESIS AND SOLVOLYSIS OF ACRIDINE 1,2-OXIDE AND 3,4-OXIDE - CRYSTAL-STRUCTURE OF ACRIDINE 1,2-OXIDE

Acridine 1,2- and 3,4-oxides were synthesized from 3,4- and 1,2-dihydroacridine, respectively, via intermediate bromohydrin acetates. Crystals of acridine 1,2-oxide were sufficiently stable to allow the first determination of X-ray crystallographic structural features of a non-K-region arene oxide. Aqueous alkaline hydrolysis of the acridine 1,2- and 3,4-oxides produced trans-1,2-dihydrorxy-1,2-dihydroacridine and trans-3,4-dihydroxy-3,4-dihydroacridine, respectively. The former dihydrodiol was also obtained by a six-step synthesis from 3,4-dihydroacridine. Acid-catalyzed hydrolysis of acridine 1,2-oxide yielded the corresponding cis- and trans-1,2-dihydrodiols (20%) in addition to 1-hydroxy- (12%) and 2-hydroxyacridine (68%). By contrast, solvolysis of acridine 3,4-oxide under acid conditions gave 4-hydroxyacridine as the exclusive product. pH-rate profiles for hydrolysis of the acridine oxides in 1:9 dioxane-water at 25 degrees C were compared with those for anthracene 1,2-oxide, naphthalene 1,2-oxide, and quinoline 5,6- and 7,8-oxides. Second-order rate constants for the hydronium ion-catalyzed ring opening of anthracene 1,2-, acridine 3,4-, and acridine 1,2-oxide are 585, 7.81, and 0.45 M(-1) s(-2), respectively, and are 3-5 times larger than the rate constants for the corresponding naphthalene 1,2-, quinoline 7,8-, and quinoline 5,6-oxides. Rate constants for uncatalyzed ring opening of anthracene 1,2- and acridine 3,4-oxides (117 x 10(-5) s(-1) and 2.4 X 10(-5) s(-1), respectively) are about two to three times larger than the corresponding rate constants for naphthalene 1,2- and quinoline 7,8-oxides, whereas the rate of nucleophilic ring opening by hydroxide ion to give the trans-dihydrodiols is accelerated by less than a factor of 2 for the acridine oxides as compared with their quinoline analogs. The pH-rate profiles for solvolysis of the acridine oxides, like those of the quinoline oxides, exhibit a pH-independent region at pH values below the pK(a) of the ring nitrogen that is attributed to formation of an unreactive N-protonated species.